Citation: Fan Yang, Jie Zhang, Jiacheng Li, Wenbo Ye, Ang Li, Weiwei He. Synthesis of a glucose conjugate of pristimerin and evaluation of its anticancer activity[J]. Chinese Chemical Letters, ;2023, 34(1): 107438. doi: 10.1016/j.cclet.2022.04.036 shu

Synthesis of a glucose conjugate of pristimerin and evaluation of its anticancer activity

Fan Yang ^{a, b} ,
Jie Zhang ^a ,
Jiacheng Li ^b ,
Wenbo Ye ^{b, c, *,} ,
Ang Li ^{b, *,} ,
Weiwei He ^{a, *,}

a.
Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China
b.
State Key Laboratory of Bioorganic and Natural Product Chemistry, Center for Excellence in Molecular Synthesis, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200032, China
c.
The Research Center of Chiral Drugs, Innovation Research Institute of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China

webye@sioc.ac.cn

ali@sioc.ac.cn

heweiwei@ecust.edu.cn

Received Date: 9 December 2021
Revised Date: 12 April 2022
Accepted Date: 12 April 2022
Available Online: 18 April 2022

Figures(2)

Taking advantage of the Warburg effect in cancer cells, glucose conjugation has emerged as a useful strategy for targeted delivery of anticancer agents. Pristimerin is a naturally occurring triterpenoid that displays potent but non-selective cytotoxicity. We developed a convergent and modular approach to construction of glucose−payload conjugates featuring copper-mediated azide−alkyne cycloaddition and prepared a glucose conjugate of pristimerin through this approach. The anticancer activity of this conjugate was evaluated in cancer cells and normal cells; however, the selectivity toward cancer cells was not significantly improved. We then examined the extracellular stability of the conjugate and found that its ester linkage was cleaved rapidly in Dulbecco's Modified Eagle's Medium at 37 ℃, which resulted in the release of pristimerin. In fact, the inorganic components in this medium were sufficient to induce the cleavage. Given that the subtle difference between intrinsic stability and extracellular stability of the conjugate linker is often underappreciated, this work highlights the importance of the latter in the development of target-selective conjugates.
- Glucose conjugation,
- Warburg effect,
- Pristimerin,
- Extracellular stability
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